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EUAs for BioNTech-Pfizer, Moderna COVID-19 vaccines, readouts from AZ and J&J could come in December

Update comes as BioNTech, Pfizer vaccine posts 95% efficacy rate in preventing COVID-19

The update comes as BioNTech, Pfizer vaccine posts 95% efficacy rate in preventing COVID-19.

Nov 19, 2020 | 2:25 AM GMT

The U.S. government is finalizing plans for review, allocation prioritization, and distribution in December of two COVID-19 vaccines in the wake of the completion of a Phase III trial of an mRNA vaccine candidate from BioNTech and Pfizer and the imminent completion of a Phase III trial of Moderna’s mRNA vaccine candidate.

“We now have two safe and highly effective vaccines that could be authorized by the Food and Drug Administration and ready to distribute within weeks,” HHS Secretary Alex Azar told reporters at a briefing Wednesday.

The briefing followed an announcement from Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) that they will file with FDA for emergency use authorization (EUA) of their BNT162b2 COVID-19 vaccine in the next few days. The companies released topline data Wednesday from a completed Phase III trial that featured a 95% (p<0.0001) efficacy rate in preventing COVID-19 that was consistent across age groups, including 94% efficacy in subjects over 65. 

Those protection rates are slightly higher than what the company saw at its interim analysis on Nov. 9 and essentially identical to the interim efficacy reported by Moderna Inc. (NASDAQ:MRNA) on Monday.

Chart compares available efficacy data from Pfizer-BioNTech and Moderna against the projected efficacy thresholds required for success of their COVID-19 vaccines as the Phase III trials progress to larger numbers of infection events. Also shown is an early interim readout from the Russian viral vector-based vaccine Sputnik V and efficacy thresholds for the two next-most advanced candidates: JNJ-78436735 from Johnson & Johnson (NYSE:JNJ) and AZD1222 from AstraZeneca plc (LSE:AZN; NASDAQ:AZN).

Moderna is expected to complete its Phase III trial of mRNA-1273 soon, Moncef Slaoui, chief scientific adviser to Operation Warp Speed, told reporters at the briefing.

FDA’s Vaccines and Related Biologic Products Advisory Committee is expected to meet in the second week of December to make recommendations about authorization of the BioNTech/Pfizer BNT162b2 COVID-19 vaccine candidate, an HHS official told BioCentury. The committee could consider an EUA application from Moderna at the same meeting or schedule one soon after, Slaoui said.

EUAs for the two vaccines may be issued by mid-December, he predicted. The maximum lag between EUAs for the vaccines will probably be ten days or less, Slaoui said.

In addition to scheduling the vaccines advisory committee meeting just a few weeks after EUAs are submitted, HHS is trying to accelerate convening of a CDC advisory committee that will recommend allocation priorities for the vaccines during the first few months when supplies will fall short of demand.  

Azar said he is working with CDC Director Robert Redfield to schedule a meeting of the Advisory Committee on Immunization Practices (ACIP) immediately after FDA issues a vaccine EUA, rather than waiting 48 hours, which is its standard procedure.

A quick allocation recommendation is important because the U.S. government plans to arrange for shipments of vaccines to start within 24 hours of an EUA, General Gustave Perna, COO of Operation Warp Speed, told reporters at the briefing.

Acceleration of the timeline will not stop with EUAs, allocation prioritization and distribution.  

Full BLA approvals could come a few months after the EUAs, Slaoui said.

Warp Speed officials confident of smooth distribution

Moderna’s vaccine and others developed with funding from Operation Warp Speed will be distributed by McKesson. Pfizer, which did not receive Warp Speed funding for R&D or manufacturing, plans to handle distribution of its vaccine.

The vaccines will be shipped to locations selected by states and other jurisdictions, such as Indian health organizations and the Bureau of Prisons, that HHS has designated.

Perna and Slaoui dismissed concerns that requirements for cold storage of mRNA vaccines will cause difficulties for states or other jurisdictions.

“We have walked through every individual step on how to maintain the Pfizer vaccine with ultra-cold refrigeration,” as well as how to maintain the vaccine in insulated boxes Pfizer is providing that can be cooled with dry ice. “My message,” Perna said, “is ‘don't be afraid of the refrigeration requirement,’ the capability exists if more is needed, the capability exists to purchase and have it delivered in a timely manner for both refrigeration and dry ice.”

Slaoui also expressed confidence in the ability of facilities that will receive vaccines to keep them at the appropriate temperature. He noted that the Moderna vaccine can be stored for 30 days at 2° to 8°C, and said that Department of Defense logistics experts have done thorough planning to ensure vaccine doses are not wasted because of a lack of proper storage. 

Unblinding trials a question of when, not if

While many of the details of COVID-19 vaccine development have been ironed out, the question of when to unblind trials is still under active discussion, Slaoui told reporters.

While the trials are designed to collect safety data for two years, there is no way that they will remain unblinded that long.

Pfizer and Moderna have said they feel ethical obligations following authorization of their vaccines to allow trial participants to learn whether they received a placebo or the vaccine and to give those who received a placebo the option to receive the vaccine.

At the time EUAs for the two mRNA vaccines have been submitted, “from the standpoint of efficacy analysis, the trials will have achieved their objectives,” Slaoui said. However, “from the standpoint of long-term follow-up, the trials could still generate substantially important information such as persistence of protection over time and safety over time.”

Operation Warp Speed, Slaoui reported, is “working with the FDA and with the companies on when to cross-over the placebo group to the vaccine, and within the placebo group, whether that crossover should happen in a staged way, depending on the prioritization, for instance, that the CDC and the ACIP would have put forward.”

Unblinding and offering trial participants the option to receive the vaccine could happen when the EUA is issued, or at some later stage such as “when 10% of the population has been immunized for a particular strata of the population that has been prioritized,” Slaoui suggested.

The latest time point for unblinding and crossover would be when a BLA is approved, he added.

Even in the absence of a control arm, it will continue to be possible to gather safety data from the trials after they are unblinded, Slaoui said.

Full approval of vaccines will “potentially have impact on recruiting subjects in other clinical trials,” he noted.

Approval of BLAs, which is expected two or three months after EUAs are issued, could make it difficult or impossible to launch new randomized, controlled COVID-19 vaccine trials in the U.S. because participants will be reluctant to accept the risk of receiving a placebo.

Slaoui called on Americans to enroll in Phase III trials of COVID-19 vaccines. “We now know that vaccination is possible, not only is it possible, but it's incredibly effective. It's very likely that the other vaccines that are being tested will also be as effective or substantially as effective. I would really ask for the population of people who want to volunteer and help to come and participate in the clinical trials, because without their participation, it's impossible to know whether more vaccines can be demonstrated to be effective and safe and made available to the population.”

In addition to altruism, he suggested that it could be in an individual’s interest to participate in a trial. In the coming months when vaccine access will be restricted to high priority groups, enrolling in a trial that provides a 50% chance of receiving a vaccine may be an individual’s best shot at getting protected.

More COVID-19 vaccine readouts on the way

In addition to the mRNA vaccines, readouts could be available soon from two adenovirus vector vaccine candidates and U.S. Phase III trials will start soon of two recombinant adjuvanted protein vaccine candidates.

“We have two vaccines that have already shown a 95% or so efficacy,” Slaoui said. “We have two more vaccines that are recruiting Phase III trials with about 11,000 subjects recruited in one and about 8,000 subjects in the other, and two more that should be starting their Phase III trials in the very near future.”

Phase III data from a trial being conducted outside the U.S. of AZD1222, the adenovirus vector vaccine AstraZeneca plc (LSE:AZN; NASDAQ:AZN) is developing in partnership with Oxford University, could be available “in the next few weeks,” Slaoui said.

Data from a Phase III trial of JNJ-78436735, an adenovirus vector vaccine that the Janssen unit of Johnson & Johnson (NYSE:JNJ) is developing, could be released “in the weeks to come maybe in early January,” Slaoui reported.

Slaoui added that U.S. Phase III trials of recombinant adjuvanted protein vaccine candidates from Novavax Inc. (NASDAQ:NVA) and from Sanofi (Euronext:SAN; NASDAQ:SNY) in partnership with GlaxoSmithKline plc (LSE:GSK; NYSE:GSK) will start soon. 

Operation Warp Speed has asked vaccine developers to defer seeking EUAs until they can produce vaccine doses at a commercial scale.

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